Kitasamycin overcomes ferroptosis and immunotherapy resistance by targeting the HUWE1-NCOA4-FTH1 Axis - PubMed
3 months ago
- #immunotherapy
- #kitasamycin
- #ferroptosis
- Kitasamycin, a macrolide antibiotic, was identified as a potent ferroptosis sensitizer in vitro and in vivo.
- Kitasamycin competitively binds to HUWE1, inhibiting its E3 ubiquitin ligase activity, stabilizing NCOA4, and activating the NCOA4-FTH1 ferritinophagy axis.
- The study found that kitasamycin induces immunogenic ferroptosis and reshapes anti-tumor T-cell immunity.
- Kitasamycin enhances immune checkpoint blockade (ICB) efficacy and overcomes ICB resistance in multiple preclinical melanoma models.
- A high NCOA4 and low HUWE1 signature correlates with ferroptosis activation, increased T-cell infiltration, and improved survival in ICB-treated patients.
- The findings suggest kitasamycin as a promising adjunct to immunotherapy for cancer patients needing concurrent antibiotic therapy.